A Purine Derivative Containing an Organoselenium Group Protects Against Memory Impairment, Sensitivity to Nociception, Oxidative Damage, and Neuroinflammation in a Mouse Model of Alzheimer's Disease

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Pinz, Mikaela Peglow ; de Oliveira, Renata Leivas ; Ramson da Fonseca, Caren Aline ; Voss, Guilherme Teixeira ; da Silva, Beatriz Pereira ; Barbosa Duarte, Luis Fernando ; Domingues, William Borges ; Ortiz, Hadassa Gabriela ; Pinto Savall, Anne Suely ; Meotti, Flavia Carla ; Alves, Diego ; Campos, Vinicius Farias ; Pinton, Simone ; Wilhelm, Ethel Antunes ; Luchese, Cristiane

• Document type: Journal article
• Source: Molecular Neurobiology; v. N/A, p. 18-pg., 2022-11-24.

Abstract

In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (A beta) (25-35 fragment), 3 nmol/3 mu l/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). A beta caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-kappa B (NF-kappa B), and the proinflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in cerebral cortex and hippocampus. Additionally, A beta increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-kappa B in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by A beta. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease. (AU)

• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/14898-2 - Investigations of the redox processes in inflammatory response and associated pathologies
• Grantee: Flavia Carla Meotti
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2